Method and system for controlling breathing

ABSTRACT

The present invention relates to a method and a system for controlling breathing of a patient. A system for controlling breathing of a patient includes a respiratory conduit. The respiratory conduit is configured to be coupled to a patient interface device and is further configured to be coupled to a pressurized air generating device. The respiratory conduit includes at least two air flow control devices, positioned between the patient interface device and the pressurized air generating device that cooperate to closely control the CO 2  levels in the patient&#39;s bloodstream through the control of the patient&#39;s respiration.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation-in-part and claims priority fromearlier filed U.S. patent application Ser. No. 13/041,783, filed Mar. 7,2011, now U.S. Pat. No. 8,485,181, issued Jul. 16, 2013, which is adivisional of U.S. Pat. No. 7,900,626, issued Mar. 8, 2011.

BACKGROUND OF THE INVENTION

The present invention relates generally to a method and system for thetreatment of breathing disorders. In particular, the present inventionrelates to systems and methods for controlling breathing of a patient bymaintaining specific levels of carbon dioxide (“CO₂”) dissolved in thepatient's arterial blood.

Sleep-disordered breathing (“SDB”) includes all syndromes that posebreathing difficulties during sleep. These include obstructive sleepapnea (“OSA”), mixed sleep apnea (“MSA”), central sleep apnea (“CSA”),Cheyne-Stokes respiration (“CSR”), and others. Some form of SDB occursin approximately 3-5% of the U.S. population.

While anatomical problems such as obesity or an abnormally narrow upperairway may be a cause of some SDB, neurological difficulties incontrolling levels of blood gases, such as CO₂ and oxygen (“O₂”), areincreasingly being recognized as important contributors to the SDBdisease process. This is especially true of the “central” syndromes,such as MSA, CSA and CSR, which may collectively account for as much as20% of all SDB. Changes in the neurological system that controls theblood gases often produce unsteady respiratory patterns that in turncause arousals from sleep. These arousals are accompanied by severespikes in blood pressure and release of stress hormones that may resultin long-term damage to a number of organ systems. Additionally, some SDBsyndromes involve abnormal overall levels of blood gases. For example,low levels of dissolved CO₂ in arterial blood are frequentlyencountered, which represents a clinical problem. Thus, there is a needto stabilize respiration and establish appropriate blood gas levels byrestoring normal control of blood gases when treating SDB.

BRIEF SUMMARY OF THE INVENTION

In this regard, the present invention provides for systems and methodsfor controlling breathing of a patient by maintaining specified levelsof CO₂ in arterial blood. The systems and methods can be used to rectifyinappropriate levels of both CO₂ and O₂ in arterial blood.

The system includes a respiratory conduit. The respiratory conduit isconfigured to be coupled at one end to a patient interface device thatis coupled to a breathing airway, e.g., nose, mouth or both, of thepatient. The respiratory conduit is configured at the opposing end to becoupled to a pressurized air generating device. The respiratory conduitincludes at least two air flow control devices, positioned between thepatient interface device and the pressurized air generating device. Therespiratory conduit includes at least two volumes, wherein one volume ispositioned between a first air flow control device and a second air flowcontrol device and another volume is positioned between a second airflow control device and a third air flow control device. Rates of flowof a gas through the first air flow control device and the second airflow control device are calculated based on an expected rate ofproduction of the gas by the patient, expected respiration rate of thepatient, expected depth of respiration by the patient, and an expectedconcentration of the gas in the air expired by the patient.

In an alternate configuration, the system includes a respiratory conduitconfigured to be coupled to a patient interface device. The respiratoryconduit is also configured to be coupled to a pressurized air supplydevice, wherein the pressurized air supply device supplies air to thepatient. The respiratory conduit includes a first valve located adjacentthe patient interface device. The first valve includes a first openingconfigured to control an escape of gas. The conduit also includes asecond valve including a second opening configured to control an escapeof gas and a first volume connector coupled to the first valve and thesecond valve. The first volume connector is configured to contain amixture of air as supplied by the pressurized air supply device and gasas generated by the patient. The conduit includes a third valve having athird fixed opening configured to control an escape of air and a secondvolume connector coupled to the second valve and the third valve. Thesecond volume connector is configured to contain a mixture of air assupplied by the pressurized air supply device and gas as generated bythe patient. The conduit includes a third connector coupled to the thirdvalve and the air supply device. In an example, the amount of gasallowed to escape from each of the three valves is determined by sizesof the valves and two volume connectors, pressure at which thepressurized air supply device operates, respiratory parameters of thepatient (e.g., depth and frequency of breathing), production of gas bythe patient per unit of time, and concentration of the gas in thepatient's arterial blood.

In one example, the system includes a respiratory conduit configured tobe coupled to a patient interface device and to a pressurized air supplydevice. The pressurized air supply device supplies air to the patient.The respiratory conduit includes a first valve located adjacent to thepatient interface device that includes a first opening configured tocontrol escape of the gas during the breathing process, a second valvethat includes a second opening configured to control escape of gasduring the breathing process; a first volume connector connecting thefirst valve and the second valve and configured to control supply of gasto the patient during the breathing process; a third valve that includesa third opening configured to control escape of gas during the breathingprocess; a second volume connector connecting the second valve and thethird valve and configured to control supply of gas to the patientduring the breathing process; a third connector connecting the thirdvalve and the air supply device. The volume of expired gas that isre-breathed (inhaled) by the patient is continuously adjusted based onan amount of gas allowed to escape from the valves and an amount of gascontained in the volume connectors.

In another example, air is supplied to the patient using a patientinterface device coupled to an air supply device using a respiratoryconduit that includes multiple controllable openings and volumeconnectors positioned along the length of the respiratory conduit. Themethod includes determining a rate of production of gas generated by thepatient. In an example, the determining also includes measuring theamount of air exhaled by the patient as well as the concentration of gasin such air. Further, the determining can include calculating initialconfiguration of sizes of multiple controllable openings and volumesusing a simulation or an estimation based on variables such as patient'sage, gender, body mass, etc. The method further includes measuring arate of flow and a concentration of gas at each of the multiplecontrollable openings; adjusting the sizes of the multiple controllableopenings based on the measuring; and adjusting the sizes of the multiplevolume connectors based on at least one of the determining and themeasuring. The air supplied to the patient includes a mixture of airsupplied by the air supply device and a gas generated by the patient.

An apparatus for controlling flow of CO₂ to a patient during breathing.The apparatus includes a CO₂ mixing device coupled to the patientinterface device. The CO₂ mixing device is configured to be coupled tothe pressurized gas device. The CO₂ mixing device includes multipleventilation orifices interchangeably connected with multiple deadspaces, wherein the multiple ventilation orifices control supply of CO₂to the patient and volume of CO₂ in the multiple dead spaces. The CO₂mixing device also includes a means for measuring airflow through eachof the multiple ventilation orifices; a means of detecting aconcentration of CO₂ in the measured airflow; a means of adjustingairflow through each of the multiple ventilation orifices based on thedetection of the content of CO₂; and a means of adjusting sizes of themultiple dead spaces based on the detection of the concentration of CO₂and the adjusting of the airflow through each of the multipleventilation orifices.

In another example, a tubing set is provides as a system for controllingthe exchange of CO₂ for a patient during breathing. The system includesa respiratory conduit. The respiratory conduit is configured to becoupled at one end to a patient interface device that is coupled to abreathing airway, e.g., nose, mouth or both, of the patient. Therespiratory conduit is configured at the opposing end to remain open tothe atmosphere or to be coupled to a pressurized air generating device.The respiratory conduit includes at least two air flow control devices,a first positioned at a predetermined point between the patientinterface device at the first end of the respiratory conduit and thesecond end of the respiratory conduit and a second airflow controldevice positioned proximate the first end of the respiratory conduit andthe patient interface. Rates of flow of a gas through the first air flowcontrol device and the second air flow control device initially setbased on an expected rate of production of the gas by the patient,expected respiration rate of the patient, expected depth of respirationby the patient, and an expected concentration of the gas in the airexpired by the patient. As expected outputs of CO₂ vary based on changesin respiration or patient metabolism, such changes are detected at thefirst airflow control device such that adjustments are made to thesecond airflow control device to bring the expected outputs of CO₂ backinto the desired range.

A method for controlling flow of CO₂ to a patient during breathing iscarried out as follows. The patient interface device is coupled to a CO₂mixing device, which is coupled to air supply device; and the CO₂ mixingdevice includes multiple ventilation orifices interchangeably connectedwith multiple dead spaces, wherein the multiple ventilation orificescontrol supply of CO₂ to the patient and volume of CO₂ in the multipledead spaces. The method includes measuring airflow through each of themultiple ventilation orifices; detecting a content of CO₂ in themeasured airflow; adjusting airflow through each of the multipleventilation orifices based on the detecting of the concentration of CO₂;and adjusting sizes of the multiple dead spaces based on the detectionof the concentration of CO₂ and the adjusting of the airflow througheach of the multiple ventilation orifices.

Further features and advantages of the invention, as well as structureand operation of various embodiments of the invention, are disclosed indetail below will reference to the accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

The present invention is described with reference to the accompanyingdrawings. In the drawings, like reference numbers indicate identical orfunctionally similar elements. Additionally, the left-most digit(s) of areference number identifies the drawing in which the reference numberfirst appears.

FIG. 1A is an illustration showing an exemplary system for controllingbreathing of a patient, according to the present invention.

FIG. 1B is another illustration showing an exemplary system forcontrolling breathing of a patient, according to the present invention.

FIG. 2A is an illustration showing exemplary clinical equipment set upusing methods and systems for controlling breathing of a patient,according to the present invention.

FIG. 2B is another illustration showing an exemplary system forcontrolling breathing of a patient, according to the present invention.

FIG. 2C is an illustration of a portion of breathing conduit shown inFIGS. 1A-2A.

FIG. 3 is an exemplary graphical representation of a relationshipbetween ventilation (i.e., the total volume of air exhaled and inhaledby the patient per minute) and CO₂ excretion by the patient usingsystems and methods for controlling breathing of a patient, according tothe present invention, along with a tracing representing a rate of CO₂production by the patient during a night.

FIG. 4 is a graphical representation of a typical CO₂ excretion by thepatient during a night.

FIG. 5 is a graphical representation of a relationship between depth ofbreathing (i.e., tidal volume) and CO² excretion during a single breathby the patient using conventional methods and systems for controllingbreathing a patient.

FIG. 6 is a graphical representation of a rate of CO₂ escaping from theapparatus for controlling breathing of a patient over the course ofeight typical breaths, according to the present invention.

FIG. 7 is a graphical representation of a comparison between normalrespiration and Cheyne-Stokes respiration.

FIG. 8 is a flow chart illustrating an exemplary method for controllingbreathing of a patient, according to the present invention.

FIG. 9 is a flow chart illustrating an alternate embodiment of a methodfor controlling breathing of a patient, according to the presentinvention.

FIG. 10 is a series of tracings showing heart rate and blood oxygensaturation through the night for a patient using conventional methodsand systems for controlling breathing.

FIG. 11 is a series of tracings showing heart rate and blood oxygensaturation through the night for a patient using a conventionalpressurized air supply machine alone.

FIG. 12 is a series of tracings showing heart rate and blood oxygensaturation through the night, according the present invention.

FIGS. 13-15 are a series of tracings indicating dead space gain inconventional breathing systems.

DETAILED DESCRIPTION OF THE INVENTION

Now referring to the drawings, the system and method for controllingbreathing is shown and generally illustrated in the figures. It isnotable that of the two blood gases, carbon dioxide (“CO₂”) and oxygen(“O₂”), problems with neurological control of breathing during sleep areprimarily related to the control of CO₂ rather than O₂. CO₂ is dissolvedin blood, and together with bicarbonate ions determines blood pH.Excessive CO₂ causes the blood to become acidic, while a deficit in CO₂will cause the blood to be alkaline. Since proteins need a stable pHenvironment in which to function, the CO₂ levels should be controlledwithin a narrow range that will yield a blood pH of about 7.4. This isaccomplished in the present invention through the close matching of CO₂excretion via the lungs to the endogenous CO₂ production that is theproduct of cellular metabolism.

FIG. 7 illustrates normal respiration and Cheyne-Stokes respirationplots along with corresponding CO₂ blood levels plots. During normalrespiration, the breathing effort of a patient is steady, as shown bythe plot 710. This corresponds to steady arterial CO₂ blood levels,shown in plot 712. A typical normal partial pressure of dissolved CO₂ inarterial blood is 40 mm Hg and O₂ pressure is approximately 105 mm Hg.During Cheyne-Stokes respiration, the patient's breathing effort iserratic, as illustrated by the waxing/waning plot 714. A correspondingplot 716 shows the associated variable blood CO₂ levels duringCheyne-Stokes respiration.

Within humans, a sensitive and finely tuned system detects blood CO₂levels via a number of sensors, or chemoreceptors, located within thevasculature and the brain of the patient. Nerve signaling from thesesensors is processed by respiratory control centers in the brain, whichin turn send appropriate breathing pattern commands to the respiratorymuscles including those of the diaphragm, chest and breathing airway.The goal of the system is to match the excretion of CO₂ with theproduction of CO₂ by varying the rate of respiration (both the depth andfrequency of breathing). In healthy individuals, this system is accurateand steady. It is able to respond quickly to changes in CO₂ productionand maintain blood CO₂ levels within a narrow range. Like manyhomeostatic mechanisms in the body, control of blood gases isaccomplished by a closed-loop negative feedback control system.

When the system for controlling blood CO₂ becomes disordered, such as inCSR, it can lose its ability to maintain steady CO₂ levels. It “chases”blood CO₂ in an oscillating pattern of “overshoot” and “undershoot”,resulting in a characteristic waxing/waning respiratory pattern. CSR isthe classic syndrome associated with this disordered respiratorypatterning and it is common in the setting of a heart failure. FIG. 7illustrates that normal breathing is accompanied by stable CO₂ levels inarterial blood while CSR exhibits oscillating breathing patterns due tounstable CO₂ levels.

Since the waxing/waning respiratory drive associated with poor controlof blood gases applies also to control of the muscles holding the airwayopen, cyclic airway collapse during the waning epoch of respiratorydrive is often a feature of these syndromes. In fact, pure waxing/waningrespiratory patterns not associated with at least intermittent airwaycollapse are relatively rare and MSA may be the dominant expression ofrespiratory instability. MSA may present as an extremely regular andpredictable pattern of obstructive events associated with reducedrespiratory effort but it may also present as a chaotic mixture ofevents of different kinds (e.g. obstructive apneas, central apneas,hypopneas) with no visually discernible pattern.

For several decades it has been possible to describe the necessaryconditions for respiratory stability in mathematical terms. Theanalytical framework is identical to that used in classical processcontrol theory for predicting the stability of a closed-loop negativefeedback control system. While these systems are able stably to controlvery complex and sensitive processes if correctly tuned, certaincategories of problems are known to cause instability and oscillatingcontrol that render the process useless or worse. In general, theseproblems are caused by an excessive sensitivity or “closed-loop gain” inthe control loop and timing problems, where an excessive time delay isencountered in measuring the results of the process and taking theappropriate corrective action. These are the same problems thatsufferers from unstable sleeping respiration often exhibit.

It is well-established that the underlying cause of instability in thechemical control of respiration is usually excessive gain or sensitivityof one of the blood gas sensors, namely the peripheral chemoreceptor.The peripheral chemoreceptor is located within the carotid artery anddirectly samples arterial blood for oxygen and CO₂ content. Thechemoreceptor is sensing the concentration of H+ ions in the blood,which is a proxy for CO₂ content in the arterial blood over a shortperiod of time. The sensing becomes disordered and sends signals to therespiratory centers in the brain that tends to overestimate changes inblood gases, specifically, CO₂. Even though the cause of the disorderedsensing is unknown, it is common in various diseases, e.g., heartfailure. It is difficult to correct the above disordered sensing usingcurrent medical technology. Further, problems with blood circulationprolong the time delay in reporting changes in blood gases, which addsto the problem of instability in the patient's respiratory control loop.

Given that increased closed-loop gain in the respiratory controlfeedback loop resulting in unstable respiration is usually due either toexcessively sensitive CO₂ sensors or impaired blood circulation, anumber of therapeutic strategies have been attempted. Most existingtherapies have various drawbacks.

Current therapeutic methods for restoring sleeping respiratoryinstability have the following problems:

1. They are complicated.

2. They are costly.

3. They are inefficient in that they may reduce one aspect of theclosed-loop respiratory control gain while increasing its other aspects.Further, they may fail to reliably reinstate conditions for stability.

4. They fail to enable a clinician to specify a target blood CO₂ rangeto be maintained during therapy where patients are currently hypocapnic.

5. They reduce an amount of oxygen available for breathing,necessitating an addition of supplemental oxygen in order to restorenormal level of blood oxygen.

6. They fail rapidly to excrete CO₂ under extraordinary circumstances,such as, after a prolonged obstructive apnea event.

7. They fail to respond immediately on a breath-by-breath basis tounstable respiratory patterns and rely on multi-breathpattern-recognition algorithms.

8. They rely on a single fixed estimate of respiratory requirementsduring the course of treatment and are not configured to adapt tovariation in respiratory requirements.

9. They rely on expensive electronic equipment.

Current methods are also unable to permit modeling of the relationshipbetween the rate ventilation of the patient and the rate of CO₂excretion in a non-linear fashion, including imposition of multipledistinct steps that permit “clamping” of respiration by maintaining CO₂excretion within a defined range under most conditions.

The system and method capable of controlling breathing of a patient bymaintaining certain levels of CO₂ in the patient's blood, whilemaintaining or improving blood oxygenation, described herein provide asolution to these problems. The present invention also provides a way tosubstantially eliminate “dead space gain”. This issue is present in someconventional breathing systems.

Unstable breathing patterns consist of alternating hyperventilation andhypoventilation or apnea. During hyperventilation, there is rapid“blow-off” of CO₂ that causes a steep drop in arterial CO₂ thatinitiates an epoch of hypoventilation or even apnea when the arterialblood reaches the peripheral chemoreceptor and the brain detects anabnormally low level of blood CO₂. During the hypoventilation, CO₂accumulates rapidly and again initiates an epoch of hyperventilation.This pattern can be repeated indefinitely.

Ideally, the lungs should be made to be less efficient duringhyperventilation in order to resist the CO₂ blow-off. One of the ways todo this is to make the patient inhale a high percentage of CO₂ ininspired air, which will interfere with gas exchange in the lungs andtherefore exhibit excessive excretion of CO₂. Likewise, the lungs shouldbe maximally efficient during hypoventilation in order to limit theaccumulation of CO₂. Thus, inhaled CO₂ is optimally zero duringhypoventilation. Any design can be characterized in terms of its abilityto exert a stabilizing influence by feeding the patient highconcentrations of inspired CO₂ during hyperventilation and none duringhypoventilation.

Unfortunately, the conventional dead space systems tend to do theopposite. As tidal volume increases, the concentration of CO₂ ininspired air decreases, thus, actually promoting instability. FIGS.13-15 illustrate that during normal breathing the dead space gains ofboth proximal single dead space design and distal single dead spacedesign are quite high. Single proximal dead space systems interpose asingle dead space volume between a sealed patient interface and a singleorifice configured to be large enough to permit flow through the orificesufficient to wash out all exhaled gases that exceed the volume of thesingle dead space. Such devices are then further connected to an airsupply device via a typical respiratory conduit. Single distal deadspace systems are configured with a single orifice substantially on ornear the patient interface and with a single conduit comprising theentire dead space acting as a coupling to the air supply device. Thesingle orifice is configured to permit a certain maximum amount of a gasto be excreted from the device and to cause substantial re-breathing ofany additional exhaled gas. High dead space gain is signified by a steeppositive slope of the function in the shaded zone. The shaded zonerepresents a range of normal breathing while using the device.

Further features and advantages of the invention, as well as thestructure and operation of various embodiments of the invention, aredescribed in detail below with reference to the accompanying drawings.The invention is not limited to the specific embodiments describedherein. Such embodiments are presented herein for illustrative purposesonly. Additional embodiments will be apparent to persons skilled in therelevant art(s) based on the teachings contained herein.

While the present invention is described herein with reference toillustrative embodiments for particular applications, the invention isnot limited thereto. Those skilled in the art with access to theteachings provided herein will recognize additional modifications,applications, and embodiments within the scope thereof and additionalfields in which the present invention would be of significant utility.

Regulation of Blood Gas Levels

Methods and systems for controlling breathing of a patient are describedherein. The methods and systems use a combination of multiple dead spacevolumes and valves to control CO₂ levels in a patient's blood and,thereby, control breathing of the patient. The device of the therapeuticsystem controls a relationship between the rate of ventilation (i.e.,total minute volume, V_(E)) and the rate of CO₂ excretion (V_(CO2))while permitting extensive modeling of this relationship in anon-linear, discontinuous fashion (See, FIG. 3 discussion below). Thissystem allows a clinician to define a level of arterial blood CO₂ to bemaintained during therapy as well as to place strong limits on bothhyperventilation and hypoventilation. Under certain circumstances, thepresent invention can increase blood oxygenation without the use ofsupplemental oxygen.

The system provides an interaction between multiple discreet dead spacevolumes and multiple ventilation orifices of either fixed(precisely-defined) or variable size, where the volumes and orifices canbe organized in a specific pattern. Such interaction offers apossibility of defining a wide spectrum of relationships between therate of ventilation and the rate of CO₂ excretion by the patient whenused in conjunction with a ventilatory assist device such as aContinuous Positive Airway Pressure (“CPAP”) machine, which is set to apredetermined pressure. In an alternate embodiment, a ventilatory assistdevice is not used and the same effect is achieved using a simple deviceinto which the patient breathes.

A respiratory conduit, which is placed between a patient interfacedevice (e.g., a sealed CPAP mask) and the CPAP machine (or any other airsupply device), has a cylindrical shape. Ventilation orifices are placedin line with the conduit to provide outflow of CO₂ that is exhaled bythe patient. The lengths of conduit lying between each ventilationorifice represent a distinct dead space or quasi-dead space volume. Asair containing CO₂ is expelled from the patient's lungs into therespiratory conduit, a pressure generated by the CPAP machine causes atleast some of the air and CO₂ contained in such air to flow out of thevarious orifices in a specific pattern. The pattern depends on thevolume of each one of patient's breaths or tidal volume (V_(T)) and thefrequency of breathing, or respiration rate. Each breath consists of anexpiratory interval and an inspiratory interval. Once the expiratoryinterval is over, inspiration commences and most or all of the remainingCO₂ in the conduit is re-breathed by the patient. Depending on thevolume of each dead space and the size of each ventilatory orifice, thecurve describing a relationship between the rate of ventilation and therate of CO₂ excretion has an arbitrary number of inflection pointsdefining line or curve segments (See, FIG. 3), each with a differentslope and length.

The above system permits extensive modeling of the relationship betweena patient's breathing (i.e., ventilation) and excretion of CO₂. Usingconventional computer simulation techniques, the sizes of orifices,volumes, and/or configuration of the two are specified to establish arelationship that serves to return the respiratory control feedback loopto a stable operation. Since during the interval prior to fallingasleep, CO₂ production may be high relative to the levels anticipated toprevail during sleep, an auxiliary ventilation valve is fitted thatpermits the patient to increase airflow through the device untilcomfortably resting in bed.

FIGS. 1A and 1B illustrate an exemplary system 100 for controllingbreathing of a patient 101. Referring to FIG. 1A, the system 100includes a respiratory conduit or a mixing device 120 configured to becoupled to mask and headgear assembly 102 and to a pressurized airsupply device or CPAP device 130. The mask and headgear assembly 102includes multiple straps 103 and a mask 104. The multiple straps 103secure the mask 104 to the face of patient 101 so that there is asubstantially sealed connection between the mask and the patient'sbreathing airway (e.g., nose or mouth). The sealed interface orconnection prevents uncontrolled leakage of air or gases from openingsthat may occur between the patient's face and the mask. In the exemplaryembodiment of FIG. 1A, one or a plurality of straps 103 are placed overupper and lower portions of the patient's head. As understood by one ofordinary skill in the art, other ways of securing the mask 104 to thepatient 101 are encompassed herein. A pressurized and/or nonpressurizedgaseous substance (including air, gas, etc.) generating device, e.g.,the CPAP device 130, can be used with the therapeutic breathing system.

The mask 104 is a sealed orofacial non-invasive ventilation mask. Forexample, the mask 104 can be a Mirage NV Full Face Mask with adjustableVELCRO® strap headgear, as manufactured by ResMed Corp., Poway, Calif. Afull-face mask can be used to cover both the nose and the mouth. Thisdesign eliminates mouth leak, permitting therapy for patients whobreathe through the mouth and/or the nose. As can be understood by oneof ordinary skill in the art, other types of masks can be used, such asa nasal mask, an oral mask, an orofacial mask, a nasal prong device, anintra-oral device, an endotracheal tube, or any other device.

The mask 104 includes a mask valve 105. The mask valve 105 can be afemale Luer fitting that includes an orifice 136 and that attaches toone of the existing Luer ports on the mask 104. The orifice 136 can bedrilled, punctured, or created by any other methods. The mask valve 105,through orifice 136, allows escape of gas (e.g., CO₂) exhaled by thepatient. Alternatively, the mask 104 does not include the mask valve105. Instead, a first valve 108 is placed on the mixing device 120,substantially adjacent to the mask 104. In one example, the orifice 136has a fixed size. This design allows a certain volume of air to escapefrom the mask valve 105 per unit of time. In another example, theorifice 136 has a variable size, which can be altered depending on theamount of air intended to be allowed to escape from the mask valve 105.In one example, the orifice 136 permits air flow of 0.5-6 liters perminute, when the mask is pressurized by the CPAP machine 130 at aspecific pressure. This pressure can be equal to the patient's CPAPpressure prescription.

Referring back to FIG. 1A, the mixing device 120 includes a first valve108, a first volume 111, a second valve 112, a second volume 113, athird valve 114, and a connector volume 115. The first valve 108includes an orifice 131. The second valve 112 includes an orifice 133.The third valve 114 includes an orifice 135. As can be understood by onehaving ordinary skill in the relevant art, the mask valve 105 can be thefirst valve 108. The mask valve 105 can be included or absent from themask 104. Also, the first valve 108 can be placed on the mask 104instead of the fitting 139.

As shown in FIG. 1A, a fitting 139 incorporates the first valve 108. Thefitting 139 is coupled to the mask 104 and the first volume 111. Thesecond valve 112 is coupled to the first volume 111 and the secondvolume 113. The third valve 114 is coupled to the second volume 113 andconnector volume 115. The connector volume 115 is coupled to thepressurized air/gas generating device 130.

The fitting 139 further includes fittings 122 and 124 through which itis coupled to the mask 104 and first volume 111, respectively. Thefittings 122, 124 can be standard type fittings having 22 mm outsidediameter (“o.d.”). To allow proper connection to the fitting 139, thefirst volume 111 can be a standard 22 mm inside diameter (“i.d.”)respiratory hose.

Further, the fittings 122, 124 can be of a swivel type to permitrotation of the fitting 139 to accommodate various positions andorientations of the mixing device 120 and provide substantially leakproof connection. Otherwise, fitting 139 can be a straight fitting or abent fitting, for example a fitting with two 22 mm o.d. ends and a90-degree bend. The first valve 108 provides an air flow of 0.5 to 6liters per minute when the system 100 is pressurized by the CPAP machine130 at a given pressure equal to the patient's CPAP pressureprescription. Fittings 126, 128 (coupling second valve 112 to firstvolume 111 and second volume 113, respectively) and fittings 132, 134(coupling third valve 114 to second volume 113 and connector volume 115,respectively) can be similar to fittings 122, 124.

The first volume 111 can be a standard 22 mm i.d. respiratory hose andcan have an internal volume of 100-400 ml depending on the desiredincrease in the patients' arterial CO₂. The hose can be a conventionalhose with rubber cuffs as used with CPAP machines; it can be acorrugated disposable respiratory hose, or it can be any other hoseappropriate for connecting mask 104 to a fitting 126.

As stated above, the second valve 112 includes a straight connectorincorporating the orifice 133 that can have a fixed size. Alternatively,the orifice 133 has a variable size. This connector can be plastic andhave 22 mm o.d. ends suitable for connection to the first volume 111 andsecond volume 113. Further, the orifice 133 location in the connector issuch that it is not obstructed by lying on a surface (e.g., a bed). Agroove in the fitting containing the second valve 112 can be created toprevent any obstructions. The orifice 133 permits airflow of 3-8 litersper minute when it is pressurized by the CPAP machine 130 at a givenpressure equal to the patient's CPAP pressure prescription.

The second volume 113 is substantially identical in type to the firstvolume 111. The second volume 113 can have a total volume of 100-400 ml.

The third valve 114 incorporates the orifice 135, which can be variableor fixed. The third valve 114 can be a straight connector, as shown inFIG. 1A. The connector can be plastic and have 22 mm o.d. ends suitablefor connection to the first volume 113 and connector volume 115. Theorifice 135 location in the mixing device 120 is such that it is notobstructed by lying on a surface (e.g., a bed). A groove in the fittingcontaining the third valve 114 can be created to prevent anyobstructions. The orifice 135 permits airflow of 15-30 liters per minutewhen it is pressurized by the CPAP machine 130 at a given pressure thatis equal to the patient's CPAP pressure prescription.

The connector volume 115 can be substantially identical in type to thefirst volume 111 and second volume 113. The length of the connectorvolume 115 can be set to accommodate placement of the CPAP machine 130in relation to the patient 101.

Each one of the orifices 131 (or alternatively 136), 133, and 135 isconfigured to allow escape of air at a specific rate when thepressurized air supply device 130 is operated at a specific pressure.Depending on the concentration of gas in the air flowing through each ofthe orifices, the gas will be escaping through each orifice at aspecific rate. The orifices can be fixed, variable, or a combination offixed and variable sized orifices can be used. As can be understood byone having ordinary skill in the art, varying locations and/or numbersof fixed and variable orifices can be used as desired. This allows apredetermined amount of air and gas (depending on the concentration ofthe gas in such air) to escape from the orifices in case of fixedorifices' sizes or a variable amount of gas to escape from the orificesin case of variable orifices' sizes. Further, in case of variableorifices, their sizes can be manually or dynamically controlled. Whenorifice sizes are manually controlled, a patient, a clinician, orsomeone else can control the size of the orifice and, thus, the amountof gas allowed to escape from the orifice. When orifice sizes areautomatically controlled, their sizes can be adjusted automaticallybased on an amount of gas exhaled by the patient, amount of gas escapingfrom each specific orifice, amount of gas contained in the volumeconnectors 111 and 113, patient physical parameters (such as bloodpressure, body mass, age, etc.) and/or other factors.

The sizes of orifices 131, 133, 135 and three volumes 111, 113, 115 canbe preliminary determined using an algorithm based on patient'sestimated high and low V_(CO2) (rate of production of CO₂ in ml perminute) as directly measured during sleep. Alternatively, the patient'sestimated high and low V_(CO2) can be derived from patient's body massor any other physiological or demographic variable or combination ofvariable. The sizes of volumes and orifices are adjusted during apolysomnographic study in a clinic, hospital, laboratory, or any otherfacility that is equipped with CO₂ monitoring equipment. Based on theadjustment, a final combination of orifices and volumes is determined.This combination establishes a first respiratory plateau (See, FIG. 3,segment 306) at or below a value of V_(CO2) equal to the minimumestimated CO₂ production per minute expected to occur during sleep and asecond respiratory plateau (See, FIG. 3, segment 310) at or above avalue of V_(CO2) equal to the maximum estimated CO₂ production perminute expected to occur during sleep.

The respiratory conduit 120 is rotatably coupled to the mask 104 and theCPAP device 130. This arrangement allows the conduit 120 to rotate ifthe patient turns during sleep. As can be understood by one of ordinaryskill in the art, the rotatable connection can be sealed to prevent anyleaks during operation of system 100.

Referring to FIG. 1B, the conduit 120 includes an anti-asphyxiationvalve 118 and any number of auxiliary valves 116 that can assist apatient during breathing. In the FIG. 1B example, the anti-asphyxiationvalve 118 and the auxiliary valve 116 are placed in the fitting 139.

The auxiliary valve 116, when opened, provides a flow of air through themixing device 120 sufficient to provide substantial washout of theexhaled CO₂ from the mixing device 120. In one example, the patient 101can operate the auxiliary valve 116 in order to provide CO₂ washoutuntil patient 101 is resting comfortably. The auxiliary valve 116 can beclosed manually by the patient 101 or automatically after a certainperiod of time elapsed.

The anti-asphyxiation valve 118 opens when the operating pressure of theCPAP machine 130 falls below a predefined value (i.e., CPAP machine 130fails to provide adequate pressure). When the latter occurs, theanti-asphyxiation valve 118 opens and allows the patient 101 to breatheambient air through the valve 118. Hence, the valve 118 preventsasphyxiation of the patient in the event of failure of the CPAP machine130.

Additionally, the mixing device 120 includes a water condensationcollection device that collects moisture from the patient's breaths.This prevents undesirable accumulation of moisture within the mixingdevice 120.

In one example, it may be determined that a male patient with a bodymass of 100 kg and a CPAP prescription of 15 cm H₂O may require thefollowing configuration of orifices and volumes:

Orifice 131  3 liters per minute First volume 113 350 ml Orifice 133  5liters per minute Second volume 115 400 ml Orifice 135  22 liters perminute

FIG. 2A illustrates an exemplary setup 200 for a polysomnographic and/ortitration study of a patient. The setup 200 includes a CO₂ monitor 204,a computing device 206, variable area flow meters 202 (a, b, c) havingneedle valve controls, a CPAP machine 212, a switchable manifold 208,tubing 210 (a, b, c), a conduit 218, and an orofacial mask 214.

The mask 214 is similar to 104 shown in FIGS. 1A and 1B. The CPAPmachine 212 is similar to the CPAP machine 130. Also, the conduit 218 issimilar to the mixing device 120. The conduit 218 connects mask 214 andCPAP machine 212. The conduit 218 is also connected to tubing 210 (a, b,c). The conduit 218 includes a first volume 211, a second volume 213,and a connector volume 215, which are similar to the volumes 111, 113,and 115, respectively. The tubing 210 a connects orifice 131 (not shownin FIG. 2A) a flow meter 202 a. The tubing 210 b connects orifice 133(not shown in FIG. 2A) to a flow meter 202 b. The tubing 210 c connectsorifice 135 (not shown in FIG. 2A) to a flow meter 202 c. The tubing 210(a, b, c) can be ⅜ inch i.d. Tygon tubing. The tubing 210 (a, b, c) canbe glued, cemented, or otherwise securely fastened to the orifices 131,133, 135 and flow meters 202 (a, b, c), respectively.

Further, the conduit 218 is configured to vary volumes 213 and 215 usingmovable pistons or cylinders (shown in FIG. 2C) located inside thevolumes 213 and 215. The cylinders can be sealed using o-ring clamps(shown in FIG. 2C). FIG. 2C illustrates a portion of the conduit 218having a cylinder/piston 236 placed in the conduit's interior 234. Thecylinder/piston 236 is able to move back and forth as shown by thebi-directional arrow A. The movement increases or decreases dead spacevolume 232. The cylinder/piston 236 is secured by an O-ring clamp 238.This cylinder/piston 236 arrangement can be placed in either or allvolumes 211, 213, and 215. The volumes can also include graduationscales (not shown in FIGS. 2A, 2C) to adjust the dead space volume 232to a specific value.

Referring back to FIG. 2A, the output sides of the flow meters 202 (a,b, c) are coupled to switchable manifold 208, which allows measurementof CO2 content in the air flowing from anyone of or a combination of thevariable flow meters 202 (a, b, c) by the monitor 204. The monitor 204is connected to the computing device 206, which collects the data. Thedata is used to adjust the rates of airflow through each of the flowmeters 202 and the sizes of the volumes, as described with respect toFIGS. 1A, 1B and 3-9.

Referring now to FIG. 2B, in one embodiment, the mixing device 120includes a first orifice 131 connected and in fluid communication with afirst control tube 161 and terminating in a first variable flow controlvalve 162, a first volume 111 that includes the collective interiorvolume of a gain chamber 163, a second orifice 133 connected and influid communication with a second control tube 164 and terminating in asecond variable flow control valve 165. A controller 166 is providedthat houses the variable flow control valves 162, 165, the computerinterface 206, and the CO₂ monitor 204. A means for establishing airflowthrough the mixing device 120 is shown as a pressurized air supplydevice 130 or CPAP. Alternately, rather than introducing pressure to themixing device 120, airflow through the mixing device 120 may beestablished by providing a vacuum pump that is connected to the outletends of the variable flow control valves 162, 165.

The second control tube 164 may preferably have its inlet locatedcentrally on the interior of the gain chamber 163. Further the inlet ofthe second control tube 164 may be a length of perforated tubing suchthat the gasses entering the second control tube inlet are an accuraterepresentation of the gasses within the gain chamber 163 itself.

In combination, the orifices 131 and 133 are configured to allow aspecific, measured rate of escaping gases based on the rates of thesupply air flow (either via pressure or vacuum) and the predictedmetabolic rate of the patient. In an initial set-up for example, theflow of gasses out of the orifices 131 and 133, via control tubes 161and 164 as controlled by control valves 162 and 165 may be set forexample at an outflow of 4 l/min. The outflowing gasses are monitored atthe CO₂ detector 204 such that the CO₂ output is preferably maintainedat 1% of the mixed gas output. More preferably, the process variable interms of percentage CO2 output is monitored via the second control tubeat the gain chamber 163. Should the CO2 output vary beyond apredetermined range, the controller 166 adjusts the flow at controlvalve 162 to either increase or decrease the outflow of gasses until theCO2 output returns to the set range.

In the case of CSR such an adjustment is made on a gradual basis as themetabolism of the patient changes instead of on a breath by breathmonitoring. However, certain disordered breathing conditions result inrandom breathing rhythms such that the present invention can operate toclamp each breath of the patient as well.

As can be understood by one having ordinary skill in the art, varyinglocations and/or numbers of fixed and variable orifices can be used asdesired. This allows a predetermined amount of air and gas (depending onthe concentration of the gas in such air) to escape from the orifices incase of fixed orifices' sizes or a variable amount of gas to escape fromthe orifices in case of variable orifices' sizes. Further, in case ofvariable orifices, their sizes can be manually or dynamicallycontrolled. When orifice sizes are manually controlled, a patient, aclinician, or someone else can control the size of the orifice and,thus, the amount of gas allowed to escape from the orifice. When orificesizes are automatically controlled, their sizes can be adjustedautomatically based on an amount of gas exhaled by the patient, amountof gas escaping from each specific orifice, patient physical parameters(such as blood pressure, body mass, age, etc.) and/or other factors.

The initial outflow allowed by control valves 162, 165 and the combinedvolume of the tubing 111 and the gain chamber 163 can be preliminarydetermined using an algorithm based on patient's estimated high and lowV_(CO2) (rate of production of CO₂ in ml per minute) as directlymeasured during sleep. Alternatively, the patient's estimated high andlow V_(CO2) can be derived from patient's body mass or any otherphysiological or demographic variable or combination of variable. Thesizes of volumes and orifices are adjusted during a polysomnographicstudy in a clinic, hospital, laboratory, or any other facility that isequipped with CO₂ monitoring equipment. Based on the adjustment, a finalcombination of flow control setting and volume is determined. Thiscombination establishes a first respiratory plateau (See, FIG. 3,segment 306) at or below a value of V_(CO2) equal to the minimumestimated CO₂ production per minute expected to occur during sleep and asecond respiratory plateau (See, FIG. 3, segment 310) at or above avalue of V_(CO2) equal to the maximum estimated CO₂ production perminute expected to occur during sleep.

Method of Treatment and Titration of a Patient

Initially, a nightly CO₂ excretory profile of a patient during sleep isdetermined. This profile is determined by measuring a total amount ofCO₂ production by the patient during a diagnostic overnightpolysomnographic study. Such profile contains information about high,low and mean levels of CO₂ production during sleep. Prior to a trialfitting of the device (See, FIGS. 1A-2) on a patient, the collected dataalong with other patient physiological data and desired therapeuticresults are used to generate a simulation model, which provides a bestestimate of a configuration of volumes and orifices to be used duringtreatment. During a subsequent polysomnographic titration study thedevice is fitted on the patient, an initial CPAP pressure is selectedand an actual CO₂ flow through each of the orifices is measured at thepredetermined air flow rate. The orifice sizes are adjusted (eithermanually or automatically) so that the CO₂ flow through or escape fromeach orifice equals a desired value depending on an intendedrelationship to the patient's CO₂ excretory profile. The volumes' sizesare also adjusted (whether manually or automatically). This depends onwhether patient's mean amount of arterial CO₂ diverges from the desiredlevel. The adjustment of sizes can be done by physically substitutingvolume hoses of known size. Alternatively, a cylinder/piston arrangement(shown in FIG. 2C) can be inserted into each of the volumes to manuallyor automatically decrease or increase the interior spaces of the volumesbased on the obtained data and desired values. In the event that it isnecessary to change the starting CPAP pressure, the procedure ofmeasuring and adjusting can be repeated to return to a specific desiredresult.

At the end of the titration study, a final configuration of CPAPpressure, volumes and airflow through each of orifices is recorded. Acustom-built conduit/mixing device (as shown in FIGS. 1A-2C) can bemanufactured according to these specifications and dispensed to apatient for use. As can be understood by one having ordinary skill inthe art, various configurations of orifices and volumes are possible.

The device and therapeutic system is tailored to each individualpatient. Initially, the patient is referred to an appropriate sleepdiagnostic facility. In the facility, a clinician orders an evaluationof a patient for possible respiratory instability. Certain modificationsand enhancements are optionally made to the usual overnightpolysomnographic study, described above. These modifications can includeadditions of end-tidal CO₂ monitoring and calibrated nasal pressuremeasurement. Alternatively, instead of nasal pressure, another highlyaccurate means of determining airflow through the patient's nose andmouth can be utilized, including wearing a respiratory mask with anattached flow sensor. The capnography 600 waveform (See, FIG. 6) andflow signals are recorded throughout the night and stored in thepolysomnographic recording system. As a result of the study, either inreal time or a post-study process, a patient's minute CO₂ volume(V_(CO2)) versus time, i.e., a rate of CO₂ excretion during sleep, isderived by multiplying the sum of the rates of airflow through theorifices and the airflow meters and the percentage of CO₂ in the air, asmeasured by the end-tidal CO₂ monitor. The patient's CO₂ excretionprofile is determined using a number of commercially available analyticpackages, such as DASYIab, manufactured by National InstrumentsCorporation of Austin, Tex.

The interpreting clinician inspects the evolution of V_(CO2) during thecourse of the night and determines the predicted low, mean, and highV_(CO2) targets for which the device should be configured. The clinicianalso inspects the end-tidal CO₂ waveform itself to evaluate theevolution of arterial CO₂ and to determine to what degree the patientwill require overall CO₂ support in order to reach a target meanarterial CO₂ level during the night. The clinician then again refers thepatient for a titration study using the present invention.

Prior to the titration study, the polysomnographic technician willobtain certain demographic and physical information about the patient inorder to establish a starting configuration. For example, age, sex, bodymass, arterial CO₂ level, estimated CPAP prescription, and actual andtarget end-tidal CO₂ values are collected. This information is then usedto make an estimate of a probable optimal configuration of orifices andvolumes. Patient's age, sex and body mass are used to derive a probablelow, mean, and high value for sleeping V_(CO2) based on at least studiesof multiple patients. Then, V_(CO2) values are used to set target flowrates for the orifices and determine the size of the orifices based onflow rates through each orifice under pressure. The size of the firstdead space volume 111 is estimated based on the desired target end-tidalCO₂. Finally, a minimum size for the third orifice 115 is estimated.This permits a washout of any overflow CO₂.

After the study is completed, the patient can be provided with ahome-use device that is similar to the system 100 shown in FIG. 1.Alternatively, the patient can be scheduled for treatment at a clinicusing the system of present invention. The device is capable of thefollowing exemplary functions

(i) measuring an airflow through each ventilatory orifice 131, 133, 135individually (conventional gauges can be used as variable area flowmeters or electronic flow meters coupled to an input/output device,e.g., a computer, can be used to measure the airflow);

(ii) detecting CO₂ content in airstreams stemming from each orifice 131,133, 135 and transmitting the collected content data to an input/outputdevice, e.g., a computer;

(iii) adjusting airflow through (or escaping from) each of the orifices131, 133, 135 using valves (the valves can be operated manually orautomatically);

(iv) adjusting sizes of the two dead space volumes by disconnecting andconnecting hoses of various lengths (alternatively, variable volumedevices can be incorporated, which permit altering the dead spacevolumes without changing hoses; the variable volume devices can benested cylinders sealed with O-rings that can slide in and out); and

(v) computing and displaying a rate of flow of CO2 through each of theorifices (this function can be performed by any computing device havingan appropriate data acquisition peripheral device running on software,such as DASYLab, which permits acquisition of both the CO2 and flow datachannels; a suitable display can be used to permit a clinician toobserve flow of CO2 through each orifice as the volumes are adjusted).

FIGS. 8 and 9 illustrate exemplary methods 800 and 900, respectively, ofcontrolling breathing of a patient in accordance with the abovediscussion and using the systems shown in FIGS. 1A-2C. Referring to FIG.8, method 800 begins with step 802. In step 802, the amount of CO₂generated by the patient is determined (high, low and mean values of CO₂production per minute by the patient are measured). Then, the processingproceeds to step 803, where the end-tidal CO₂ tracing for the night isinspected to determine the magnitude of a desired increase in the meanarterial CO₂ during therapy. In step 804, the optimum CPAP pressurelikely to treat any existing obstructive apnea is determined. Then, insteps 805 and 806, a preliminary configuration of the system 100 isdetermined using the data gathered in steps 802-804. To configure thesystem, a computer simulation of the performance of the system undervarious assumptions can be used. Alternatively, empirically determinedvalues for the orifices and volumes that are a function of the datagathered in steps 802 and 804 in addition to patient's physiologicaland/or demographic data can be used. In step 806, a rate of flow andconcentration of gas at each of the multiple controllable openings ismeasured. In step 807, patient's arterial CO₂ level is measured. Then,in steps 808-809 the sizes of the orifices, volumes, and optionally CPAPpressure are adjusted. Steps 808-809 can be repeated until a specificconfiguration of orifices, volumes and CPAP pressure is reached.

Referring to FIG. 9, method 900 begins with step 902, where airflowthrough each of the ventilation orifices is measured. In step 904, thecontent of CO₂ in the airflow, measured in step 902, is determined. Themethod then proceeds to step 906. In step 906, the airflow is adjustedthrough each of the multiple ventilation orifices based on thedetecting, performed in step 904. In step 908, the sizes of the deadspace volumes are adjusted also based on the detecting of step 904 aswell as the adjustment of the multiple ventilation orifices performed instep 906.

As can be understood by one having ordinary skill in the art, the abovemethods can be applied in a laboratory setting, a hospital, a clinic, atpatient's home, or any other facility.

FIG. 3 illustrates a relationship 300 between the various dead spacevolumes and orifices which permits an extensive modeling of the rate ofexcretion of CO₂ (V_(CO2)) by the patient with respect to various ratesof ventilation (V_(E)). In an embodiment, the present invention includestwo dead space volumes 111 and 113 and three ventilation orifices131,133,135 that cause various changes in the slope of FIG. 3.

In FIG. 3, curve 302 represents a nightly CO₂ excretion profile of apatient which is overlaid on the plot to illustrate the range of likelyCO₂ excretion rates by the patient. Referring to FIG. 4, the horizontalaxis of the plot represents time in minutes and the vertical axisrepresents a rate of production of CO₂ by a patient per minute, asmeasure in milliliters per minute (ml/min). Referring back to FIG. 3,the horizontal axis represents patient's rate of ventilation (V_(E)),measured in ml/min, and the vertical axis represents the rate ofexcretion of CO₂ (V_(CO2)) by the patient in ml/min when the presentinvention's system is used. A typical relationship between these twoquantities, when the present invention's system is not used, is definedas follows:

V _(CO2)−(V _(E) −V _(D))*(FA _(CO2) −FI _(CO2))  (1)

where V_(D) is equal to the sum of the physiological and artificiallyadded volumes of dead space multiplied by the respiratory frequency;V_(E) is equal to the total volume of air inspired and expired duringeach breath multiplied by the respiratory frequency, FA_(CO2) is thepartial pressure of dissolved CO₂ in arterial blood divided by anambient air pressure; FI_(CO2) is a fractional concentration of CO₂ inthe air inspired by the patient. The function described in equation (1)is represented by a straight line that intersects a horizontal axisabove zero.

Referring back to FIG. 3, the curve 320 describes a relationship betweenV_(E) and V_(CO2) according to the present invention, and includes thefollowing segments: hypoventilatory traverse segment 304, firstrespiratory plateau segment 306, eucapnic traverse segment 308, secondrespiratory plateau segment 310, and hyperventilatory traverse segment312. Each segment has a specific slope and length defined by the numberand size of dead space volumes and orifices placed in the respiratoryconduit as well as volume of CO₂ flowing through the dead space volumesand orifices. Thus, the number of segments varies with the number ofdead space volumes and orifices in the conduit.

As shown in FIG. 3, the hypoventilatory traverse segment 304 is causedby the placement of the first orifice in the respiratory conduit. Theslope of the segment illustrates a normal relationship between breathingand CO₂ excretion described in equation (1) until a saturation point isreached. The saturation point that corresponds to a maximum rate of CO₂flow through the first orifice is represented as the junction of thesegment 304 and segment 306.

This hypoventilatory traverse describes a relationship betweenventilation and CO₂ excretion while the patient is hypoventilating. Atvalues of V_(CO2) below the estimated minimum sleeping level, therelationship between V_(E) and V_(CO2) is substantially unchanged fromthe normal physiological relationship. One of the destabilizing elementsin unstable respiratory syndromes is the rapid accumulation of blood CO₂during epochs of hypoventilation. Due to the inherent time delay inexecuting the control loop, overshoot is inevitable when this happensand the accumulation will quickly result in blood CO₂ levels that aresubstantially above normal. The system described herein substantiallyminimizes any CO₂ build-up and provides sufficient ventilation to expelall exhaled CO₂ during hypoventilation immediately through the orifices.The size of the first orifice together with the configuration of theother orifices and dead space volumes as well as patient's respiratoryparameters determines the value at which the relationship betweenV_(CO2) and V_(E) begins to depart from normal values. The first orificeis sufficiently large to place this first inflection point in the curve320 at or just below the minimum expected sleeping V_(CO2) (See, FIG.3).

The first respiratory plateau segment 306 represents the effect ofplacing a first dead space volume in the respiratory conduit. Once thefirst orifice reaches the saturation point, it does not matter how muchthe patient increases ventilation until such increase overcomes thefirst dead space volume by pushing expired CO₂ beyond the first deadspace volume and past the second orifice. Hence, increases inventilation do not result in any additional CO₂ excretion until thispoint is reached. The rate of ventilation at which the first dead spaceis overcome and CO₂ can flow from the second orifice is defined at thejunction of the segment 306 and segment 308.

This respiratory plateau includes a zone where increased respirationabove the first inflection point in the curve results in virtually noincrease in V_(CO2). This segment has a slope substantially near zero.The existence of this respiratory plateau is due to the fact that thefirst dead space volume is larger than the volume of gas that can beexpelled through first orifice during the duration of a typical breath.The remaining volume of CO₂ is re-inhaled. Any additional CO₂ volumewithin the first dead space volume does not result in increased levelsof excreted CO₂. The onset of an unstable respiratory cycle oftencommences with a progressive narrowing of the airway, resulting indecreasing V_(E). The instability may further develop if decreases inV_(E) are accompanied by proportional decreases in V_(CO2). This givesrise to a build-up of CO₂ in the blood sufficiently rapid to cause“overshoot” before the brain can respond to the build-up. The existenceof the first respiratory plateau serves to maintain CO₂ excretion at asteady level in the face of substantial decreases in V_(E), thus,avoiding a rapid CO₂ build-up and preventing substantial “overshoot” asthe brain has time to respond to the decrease in ventilation. Whenrecovering from an epoch of low or no ventilation, the first respiratoryplateau prevents the increase in CO₂ excretion from increasingproportionally to the increase in ventilation. In a similar fashion,this places an obstacle in front of excessive CO₂ blow-off that posesthe possibility of “undershoot.”

The first respiratory plateau segment 306 also permits the clinician tospecify a mean arterial level of CO₂ for the patient during sleep. Sinceaffected patients are typically at least slightly hypocapnic (i.e.,having lower than normal CO₂ in arterial blood), it is desirable toreset their sleeping CO₂ levels to a value that is closer to normal. Thelength of the first respiratory plateau segment 306 determines blood CO₂during therapy. Further, since the segment 306 is generated as a resultof existence of the first dead space volume in the mixing device,increasing the size of the first dead space volume will raise blood CO₂levels. The amount by which any such increase in volume will raise bloodCO₂ levels can be calculated based on the patient's collected data.

The eucapnic traverse segment 308 represents placement of a secondorifice or gain chamber in the respiratory conduit. Until this orificeis saturated (i.e., the point at which the concentration of CO₂ in theair flowing from the orifice reaches a maximum), increases in the rateof ventilation (V_(E)) result in increases in the rate of CO₂ excretion(V_(CO2)). The saturation point of the second orifice is defined at thejunction of the segment 308 and 310.

Further, segment 308 represents the relationship between V_(E) andV_(CO2) in the range of expected sleeping V_(CO2). Segment 308 is astraight line having a slope that is substantially less than that of thehypoventilatory traverse segment 304. The slope of this relationship asit passes through the actual rate of CO₂ production by the patient at agiven time establishes the conditions for respiratory stability. Theslope is a variable in the relationship describing a closed-loop gain inthe respiratory control feedback loop. Since the gain in the controlbecomes excessive in unstable respiratory syndromes, reducing the slopeof the segment 308 in an immediate vicinity of a point where CO₂production and excretion match (i.e., eucapnia) stabilizes respiration.

The slope of the eucapnic traverse segment 308 is governed by multiplevariables, such as the first and second dead space volumes and sizes ofthe first and second ventilator orifices. The slope of segment 308becomes shallower when larger dead space volumes are used and where thesaturation points of the first and second orifices are closer together.The range of V_(CO2) traversed is also determined by the size of thesecond orifice 133. The measurement of patient's sleeping V_(CO2)permits setting the first respiratory plateau segment 306 at the highestappropriate V_(CO2) level and making the length of the eucapnic traversesegment 308 as short as possible. This achieves a shallow slope of thesegment 308.

The second respiratory plateau segment 310 is similar to the firstrespiratory plateau segment 306, however, segment 310 representsplacement of a second dead space volume in the respiratory conduit. Theeffects produced are similar to those discussed above with respect tosegment 306. The saturation point of the second dead space volume isdefined at the junction of the segment 310 and 312.

The second respiratory plateau segment 310 is disposed above the highestexpected sleeping value of V_(CO2) and functions in a manner similar tothat of the first respiratory plateau segment 306. It is also a linesegment with a nearly zero slope and constitutes a zone where changes inV_(E) result in little or no change in V_(CO2). The length of the secondrespiratory plateau segment 310 is determined by the volume of thesecond dead space. It inhibits CO₂ excretion during hyperventilation, assharp increases in ventilation result in little or no increase inV_(CO2).

The first and second respiratory plateaus segments 306, 310 provide apowerful “ventilatory clamp.” While V_(CO2) can vary outside of the zonedetermined by the two plateaus 306,310, it will do so in response to avery strong stimulus, e.g., a need to excrete CO2 rapidly after aprolonged obstructive apnea.

The hyperventilatory traverse segment 312 represents placement of an“escape” valve or a third orifice in the respiratory conduit. The thirdorifice is larger than the other two orifices. This allows escape of CO₂after saturation of the first and second orifices and dead spacevolumes. As can be understood by one having ordinary skill in the art,other configurations of orifices and dead space volumes are possible,thus, resulting in a different graphical representation.

The hyperventilatory traverse segment 312 serves as a safety precautionin the event that it will be necessary to excrete CO₂ at a higher thanexpected rate, e.g., after a lengthy obstructive breathing event. Suchexcretion generates vigorous breathing at rates that are twice or morethe normal rate of ventilation required to achieve such V_(CO2) levels.Without the hyperventilatory traverse there is a risk of developing atleast temporary respiratory acidosis under some circumstances. Thehyperventilatory traverse is created by the third orifice 135, which canbe larger than orifices 131 and 133. The size of the orifice 135 isdetermined by the ability of the CPAP machine 130 to maintain pressureat maximum flow rates likely to be encountered during treatment. In anembodiment, the orifice 135 is made as large as possible withoutovertaxing the CPAP machine.

FIG. 6 illustrates a tracing 600 the concentration of CO₂ in the airflowing out of all of the orifices of the system together over thecourse of eight breaths. In this tracing the system is correctlyadjusted and a characteristic “hip” 612 develops in the waveform. Theexistence of this hip is due to the elimination of all exhaled CO₂ fromthe second dead space at a point in the breathing cycle and thus acessation of all CO₂ flow through the second orifice. Since significantCO₂ remains in the first dead space and in fact the first orificeremains saturated for a further period of time, the flow of CO₂ remainsbriefly at the level of the hip until the first dead space is fullyexhausted. The lack of a hip is an indication that the first orifice istoo large and the emergence of a second hip is an indication that thefirst and second orifices taken together are too small. Thus, the systemmay be tunable with reference to the morphology of this waveform.

FIGS. 10-11 illustrate tracings of a heart rate (respective upperportions of the figures) and blood oxygen saturation levels (respectivelower portions of the figures) for a patient during a night. Thesegments of the heart rate tracings containing dense spikes indicatedisturbed or fragmented sleep due to frequent arousals originating froma respiratory anomaly. The segments of the heart rate tracings notcontaining frequent spikes indicate restful or consolidated sleep. FIGS.10 and 11 illustrate that the affected patient actually gets very fewand short periods of consolidated sleep during the night usingconventional methods and systems for controlling breathing.

FIG. 12 illustrates tracings of heart rate and blood oxygen saturationusing the systems and methods discussed in FIGS. 1A-9. The devicesubstantially resolved the frequent arousals, permitting long periods ofrestful, consolidated sleep. This results in an improvement of symptomsand is indicated by the existence of far fewer spikes in the heart ratetracings, as well as a virtually fixed oxygen tracing. Further, thesystem described herein has increased the patient's blood oxygensaturation to a level nearly the same as that in FIG. 10, where threeliters per minute of supplemental oxygen were being given. The oxygenlevels indicated in FIG. 12 were achieved using only the system and nosupplemental oxygen. These data indicate that the therapeutic systemeffectively and reliably eliminates arousals caused by breathinganomalies while maintaining very favorable blood oxygen levels. Thisprovides substantial symptomatic relief to affected patients.

In an exemplary setting, the present invention allows for 2-2.5%improvement in oxyhemoglobin saturation in a patient as compared to freebreathing of ambient air. Since the oxyhemoglobin saturation curve isflat at its high end, this represents an important increase in availableoxygen at the perfused tissues. Further, the present inventionpotentially obviates a need for supplemental oxygen in a number ofmedical settings. Also, by increasing oxygenation the present inventionmay reduce the sensitivity of the peripheral chemoreceptor, which causesmost periodic breathing syndromes.

The present invention forces an increase in the depth of breathing and,thus, the overall rate of ventilation, since the first orifice isconfigured to saturate at a level that is insufficient to permitexcretion of all CO₂ being produced by the patient. The patient breathesdeeply enough to push CO₂ through the first dead space volume, so thatCO₂ exits the device through at least the second orifice or at the gainchamber. By the time patient's inspiratory interval commences, theexhaled gas in various dead space volumes has been replaced with airand, thus, the concentration of oxygen in the inspired air is onlyslightly lower than that in the ambient air. Taking the two thingstogether, the increase in breathing more than offsets the slight declinein oxygen content of inspired air (F_(IO2)) to produce greater oxygentransport in the lungs. Conventional single proximal dead space producesa decrease in F_(IO2) that more closely matches or exceeds the increasein ventilation and therefore, a frequent need for supplemental oxygen.This is because the dead space is filled with exhaled breath and remainsfilled until inhalation commences. Conventional single distal dead spaceneither increases ventilation nor decreases F_(IO2) versus normalbreathing, thus, there should be no change in oxygen saturation.

The present invention, as described with respect to FIGS. 1A-12, can beused in the following areas:

1. Recovery from carbon monoxide poisoning. The systems and methods ofthe present invention speed up the rate of clearance of CO by three tofive times relative to the conventionally available methods (e.g.,giving oxygen).

2. Prevention of hypocapnia during birth. Hyperventilation by thedelivering mother is very common and cuts oxygen supply to the fetussubstantially due to a sharp drop in CO2. Low CO2, or hypocapnia,inhibits oxygen transport in many ways. The present invention improvesoxygen flow to the fetus during delivery.

3. Recovery from altitude sickness/mountain climbing. The presentinvention systems and methods without use of the CPAP machine allowsquick recovery from this condition.

4. Recovery from ventilator dependency. It is often difficult to weanpatients from ventilator dependency, which is a cause of death in acritical care setting. The present invention stimulates breathing andincreases oxygenation of the patient allowing the patient to quicklyrecover.

5. Recovery from anesthesia. This is similar to the recovery fromventilator dependency.

6. Obviating the use of supplemental oxygen in certain chronic lungdiseases. Chronic obstructive pulmonary disease is very common andrequires expensive oxygen therapy. However, with the present inventionthere is no need to use such oxygen therapy.

7. As can be understood by one having ordinary skill in the art, otheruses of the present invention's systems and methods are possible.

Example embodiments of the methods, circuits, and components of thepresent invention have been described herein. As noted elsewhere, theseexample embodiments have been described for illustrative purposes only,and are not limiting. Other embodiments are possible and are covered bythe invention. Such embodiments will be apparent to persons skilled inthe relevant art(s) based on the teachings contained herein. Thus, thebreadth and scope of the present invention should not be limited by anyof the above-described exemplary embodiments, but should be defined onlyin accordance with the following claims and their equivalents.

What is claimed:
 1. A system for controlling breathing of a patientcomprising: a patient interface that is received in communication withthe patient's airway; a mixing device extending from the patientinterface, the mixing device comprising: a first orifice connected toand in fluid communication with a first control tube and terminating ina first variable flow control valve; a second orifice connected to andin fluid communication with a second control tube and terminating in asecond variable flow control valve; a first volume extending betweensaid first and second orifices; and a controller, wherein a volume ofexhaled gasses from said patient is controlled with said first andsecond variable flow control valves.
 2. The system of claim 1, whereinsaid controller includes a CO₂ detector said controller adjusting atleast one of said first and second variable flow control valves inresponse to a reading at said CO₂ detector.
 3. The system of claim 1,wherein said controller includes a CO₂ detector said controllerpredicting a metabolic rate of said patient based on the CO₂concentration in said exhaled gasses said controller adjusting at leastone of said first and second variable flow control valves in response tosaid metabolic rate.
 4. The system of claim 1, said first volumecomprising a gain chamber at said second orifice.
 5. The system of claim1, further comprising: a means for establishing an airflow through saidmixing device.
 6. The system of claim 5, said means for establishingairflow through said mixing device comprising a pressurized air supplydevice.
 7. The system of claim 5, said means for establishing airflowthrough said mixing device comprising a vacuum pump.
 8. The system ofclaim 1, wherein said controller monitors a process variable via thesecond control tube and adjusts the first control valve to increase ordecrease the flow therethrough until the process variable returns to apredetermined range.
 9. The system of claim 8, wherein said processvariable is CO₂.